Anticonvulsants as Mood Stabilizers: Mechanism and Side-effect
Anticonvulsants as Mood Stabilizers Examples: Valproate, Carbamazepine, Lamotrigine
Pharmacology
Mild anticholinergic effect
Drowsiness, dry mouth, blurred vision, constipation
Allergic reaction
Benign rash
Pharmacokinetics —■ Cleared from circulation by liver —■
Pharmacodynamics Block voltage sensitive sodium channels
Failure to clear reactive metabolites
• T-cell mediated cytotoxic reaction to drug antigens Potentially life threatening –Stevens-Johnson Syndrome
• NI, Glutamate and aspartate release or I` GABA neurotransmission
Authors: Usama Malik Reviewers: Sina Marzoughi Aaron Mackie* * MD at time of publication
Dose adjustments needed in setting of liver disease and specific CYP450 inhibitors/inducers
Excessive blockage of VSSCs
Abrupt discontinuation or 4, intake Inhibition of dopaminergic activity Neurologic effect Systemic effect 1 1 •
Withdrawal seizure, relapse of bipolar disorder
Notes: • Valproate relies on CYP450 2C9/2C19, Carbamazepine relies on CYP450 34A, and Lamotrigine relies on glucuronidation • Lamotrigine and Carbamazepine are excreted renally • Valproate act on nonspecific VSSCs while lamotrigine and carbamazepine mostly act on alpha unit VSSC • Exact mechanism for some of the side-effects is unknown
Legend: Pathophysiology Mechanism
Dose-dependent tremor, ataxia, asthenia
Sedation, dose-Nausea, vomiting, dependent tremor, diarrhea, dizziness, diplopia, hyponatremia, rash, ataxia, asthenia, pruritus, weight gain, headache alopecia (unusual), thrombocytopenia
Abbreviations: • VSSCs: Voltage-Sensitive Sodium Channels